HLA alleles association with changes in bone mineral density in HIV-1-infected adults changing treatment to tenofovir-emtricitabine or abacavir-lamivudine

Hila Haskelberg, Damien V Cordery, Janaki Amin, Anthony D Kelleher, David A Cooper, Sean Emery, STEAL Study Group, Anthony Allworth, Jonathan Anderson, David Baker, Mark Bloch, Mark Boyd, John Chuah, David Cooper, Stephen Davies, Linda Dayan, William Donohue, Nicholas Doong, Dominic Dwyer, John Dyer, Robert Finlayson, Michelle Giles, David Gordon, Mark Kelly, Nicholas Medland, Richard Moore, David Nolan, David Orth, Jeffrey Post, John Quin, Tim Read, Norman Roth, Darren Russell, David Shaw, David Smith, Don Smith, Alan Street, Ban Kiem Tee, Ian Woolley, Hila Haskelberg, Damien V Cordery, Janaki Amin, Anthony D Kelleher, David A Cooper, Sean Emery, STEAL Study Group, Anthony Allworth, Jonathan Anderson, David Baker, Mark Bloch, Mark Boyd, John Chuah, David Cooper, Stephen Davies, Linda Dayan, William Donohue, Nicholas Doong, Dominic Dwyer, John Dyer, Robert Finlayson, Michelle Giles, David Gordon, Mark Kelly, Nicholas Medland, Richard Moore, David Nolan, David Orth, Jeffrey Post, John Quin, Tim Read, Norman Roth, Darren Russell, David Shaw, David Smith, Don Smith, Alan Street, Ban Kiem Tee, Ian Woolley

Abstract

Background: There are limited data regarding the influence of human leukocyte antigen (HLA) polymorphisms on reduced bone mineral density (BMD). We investigated the relationship between HLA supertypes and BMD in HIV-infected adults changing their existing treatment to tenofovir-emtricitabine (TDF-FTC) or abacavir-lamivudine (ABC-3TC) in the STEAL study.

Methods: Lumbar spine and right hip BMD were measured by Dual-energy X-ray absorptiometry (DXA). HLA genotypes at the 2-digit level were classified into class I and II supertypes. Student's t-tests were used to test the association between HLA supertypes and changes in hip and spine BMD over 96 weeks for the whole cohort and stratified by randomised groups. The relationship between HLA supertypes and BMD was also assessed in the subgroup of participants that were naïve to both ABC and TDF at study entry.

Results: Class II supertypes were mainly associated with hip BMD change. Overall, compared to participants not carrying HLA-DQ3, participants expressing DQ3 had less bone loss over 96 weeks at both the hip and spine (hip: 0.003 vs. -0.006 g/cm2, 95%CI 0.002 to 0.017, p = 0.016; spine: 0.006 vs. -0.006 g/cm2, 95%CI 0.001 to 0.023, p = 0.041). In participants that were naïve to both ABC and TDF at baseline and randomised to TDF-FTC, DQ3 was significantly associated with less bone loss compared with those not carrying DQ3 (hip: 0.001 vs. -0.032 g/cm2; diff 0.033; 95%CI 0.017 to 0.049; p<0.001; spine: 0.007 vs. -0.023 g/cm2; diff 0.035; 95%CI 0.014 to 0.056; p = 0.001).

Conclusions: In this cohort of HIV-infected adults, there was an association between bone status and HLA supertypes, particularly HLA-DQ3.

Trial registration: Clinicaltrials.gov NCT00192634.

Conflict of interest statement

Competing Interests: Sean Emery is a PLOS ONE Editorial Board member. This does not alter adherence to PLOS ONE Editorial policies and criteria. Hila Haskelberg, Damien Cordery and Janaki Amin declare no conflict of interest. Anthony Kelleher has received travel grant support from Merck Research Laboratories on two occasions since 2010 and from ViiV for consultancy work. David Cooper has received grants and consultancies and Honoraria from Gilead and ViiV. Sean Emery has received research grant support from Abbvie, Gilead Sciences, Merck Research Laboratories, Pfizer, and ViiV Healthcare. This does not alter adherence to PLOS ONE policies on sharing data and materials.

Figures

Figure 1. Patient disposition.
Figure 1. Patient disposition.
* Some patients were ineligible for more than one reason.
Figure 2. Absolute change over 96 weeks…
Figure 2. Absolute change over 96 weeks in hip BMD by HLA-DQ3 supertype and randomisation in participants naïve to both ABC and TDF at study entry.
Figure 3. Absolute change over 96 weeks…
Figure 3. Absolute change over 96 weeks in spine BMD by HLA-DQ3 supertype and randomisation in participants naïve to both ABC and TDF at study entry.

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